DRUGS ACTING ON

BLOOD
I. Haematinics
II. Coagulants
III. Anticoagulants
IV. Fibrinolytics (Thrombolytics)
V. Antifibrinolytics
VI. Antiplatelet drugs (Antithrombotics)
 Hemostasis is the spontaneous arrest of bleeding from the damage blood vessels.

 Clotting factors are proteins synthesized by liver.

Coagulants / haemostatics -

 The drugs arrest bleeding by vasoconstriction or promotes blood coagulation.

 Can be used as locally/systemically.

 Used to control & treat haemorrhagic states.

 Local hemostatics - styptics.

Styptics- used in bleeding sites.

Adrenaline (1:10,000 soln)- tooth sockets & nasal packs.

Thrombin dusting powder- skin grafting.
Fibrin (human plasma) - used in covering/packing bleeding surfaces.
Gelatin- with thrombin to control bleeding wounds.
Thromboplastin powder- used in surgery.
Astringents like ferric chloride, tannic acid are used in bleeding gums / sites.
Coagulants used systemically-
 Vit K- fat soluble & essential for synthesis of clotting factors (Prothrombin & factors II, VII, IX & X) by
the liver.
 Vit.K3- synthetic compound used therapeutically.
 Uses of Vit.K1 (i.v, s.c, i.m & orally)
1. Obstructive jaundice with haemorrhagic symptoms.
2. Treatment of Vit.k deficiency due to prolonged antimicrobial therapy.
3. In neonates to preventive bleeding as the intestinal flora is not developed.
4. To control bleeding due to oral anticoagulant therapy.
5. Salicylate poisoning with haemorrhagic complications.
 Fresh plasma/ whole blood is used coagulation disorders as it contains all the C. factors.
 Concentrated plasma fractions like fibrinogen, factors II, VII, VIII, IX & X are available for the
treatment of specific deficiencies (hypo fibrinogenaemia, haemophiliacs, Von williebrand’s disease).
Anticoagulants- these drugs either prevent or reduce the blood coagulation.
Classification-
(I) Anticoagulants used in vivo-
1) Parenteral anticoagulants -
a) Indirect thrombin inhibitors- Heparin, Low-molecular heparins (Enoxaparin, dalteparin) & Fondaparinux.
b) Direct thrombin inhibitor- Lepirudin, bilvalrudin & argatroban.
2) Oral anticoagulants-
Warfarin, Dicumarol, Pheninodione, Dabigatran & Rivaroxaban.
(II) Anticoagulants used in Vitro-
Heparin, Sod.citrates, sod.oxalates & sod.edetate.
Heparin-
 Discovered by a medical student Mclean.
 Latter isolated & identified by a Howell as a sulphated mucopolysaccharide.
 It’s a strongest organic acid & commercially obtained from ox lungs & pig intestinal mucosa.
 Powerful anticoagulant (both in vivo & vitro).
 M.A.O- It binds & forms a complex with plasmin antithrombin III.
 Activated antithrombin III which binds to C.F ( Xa, IIa, IXa, XIa, XIIa, XIIIa ).
 Heparin+ antithrombin III complex  X activated above clotting factors.
 Heparin binds to both thrombin & antithrombin because of long molecular structure.
 Low conc- selectively X the conversion of prothrombin to thrombin  prevents thrombus/clot
formation.
 High doses- Anti-platelet action  promotes bleeding.
 It releases lipoprotein lipase  breakdown TGs  clears plasma lipids.
Heparin p.k-
 Not effective orally, Given IV/SC.
 IM- causes hematomas.
 I.V inj- Quick onset of action, peak in 5-10min & C.T returns to normal by 2-4hr’s.
 Rx is to be monitored by aPTT or CT at high doses only
 Metabolised by liver heparinise.
 Don’t cross BBB & placental barrier.
Heparin A/e’s- Bleeding, hypersensitivity, thrombocytopenia, alopecia & osteoporosis.

Heparin over dosage- Continues bleeding.

 Mild cases - stop heparin adm., as it’s a short acting.

 Sever cases - Protamine sulphate (heparin antagonist)

 Protamine should be given I.V- 1mg neutralizes 100 U of heparin.

 Its self acts as a weak anticoagulant- so protamine avoid overdose.

 It a strong basic protein which binds & neutralises strong acids by forming stable complexes.
 Complex doesn't have anticoagulant activity.
 Whole blood transfusion is required.
• Low molecular weight Heparins- Enoxaparin, dalteparin & Reviparin etc.,
• LMWHs are obtained from standard heparin by fractionation.
• LMWHs produce anticoagulant effect by inhibition of factor Xa through antithrombin III.
• They don’t bind to both thrombin and antithrombin simultaneously bcz of short length & they have little
effect on thrombin inhibition.
• LMWHS therapy doesn’t require the aPTT monitoring but pts with chronic renal failure may need
monitoring by measuring Xa, which is excreted through urine.
• Anticoagulant effect of LMWH are not completely reversed by protamine sulphate.
• LMWH are given S/c.
Advantages of LMWH-
• Have higher s.c bioavailability as compared to UFH.
• Longer acting-once daily.
• Don’t require aPTT monitoring.
• Less incidence of thrombocytopenia & osteoporosis as compared to UFH.
 Parenteral Indirect Thrombin inhibitors
Fondaparinux Synthetic & long acting parenteral anticoagulant.
(s.c) Binds to antithrombin & selectively X factor Xa without any effect on thrombin.
Use- Pulmonary embolism & DVT.
Parentral Direct Thrombin inhibitors

Lepirudin Recombinant hirudin.

(i.v) Used as anticoagulant in pts with heparin induced thrombocytopenia (HIT).
Requires aPTT monitoring & No antidote available
Argatroban Rapid & shorting acting
(i.v) Used in HIT pts.
Requires aPTT monitoring
Bivalirudin MOA is similar to lepirudin & but actions are reversible.
(i.v)
Oral Anticoagulants-
 Warfarin – is most commonly used & vit.k antagonist.
 MOA-Anti coagulant action is by interfering with synthesis of Vit K dependent clotting factors
(II, VII, IX & X) in liver.
 It’s structurally similar to vit.k & competitively X epoxide reductase enzyme, thus producing
anticoagulant effects.
 Onset & duration of anticoagulant effect depends upon the half-lives of clotting factors.
 It shows delayed onset of anticoagulant action.
 Acts only in-vivo.

 Over dosage- haemorrhage is main hazard.

 A/e’s- bleeding, teratogenic, skin necrosis, diarrhoea & alopecia.

Warfarin toxicity- treatment depends on severity.

 Stop anticoagulant therapy.

 Fresh blood transfusion

 Antidote- Vit.K1 helps in activation of clotting factors.

 Vit.K i.v adm- response develops after several hours.

 In emergency- fresh whole blood encounters the effects of anticoagulant.

Uses of anticoagulants-
 They prevents extension of thrombus but can’t destroy the clot which is already formed.
 Heparin is a short & fast acting- for starting Rx .
 Warfarin is a long & slow acting- for maintenance Rx & oral use
1. Venous thrombosis & pulmonary embolism.
2. Post operative, post stroke & bed ridden pt’s.
3. Rheumatic valvular diseases.
4. Unstable angina- reduces the risk of MI.
5. Vascular surgery, artificial valves & haemodialysis
 Heparin Warfarin
Naturally occurring, animal source- beef, lung, pig Synthetic

Active in Vivo & in Vitro In Vivo

Adm parentally I.V/S/C Adm Orally
Acts by + antithrombin III & inactivates X a, II a, IX Acts by inhibiting Vit-K dependent
a, XI a, XII a, XIII a clotting factors II, VII, IX & X

Rapid onset action & short duration Slow onset & long acting

Monitored by aPTT Monitored by INR

Over dosage- Protamine Over dosage by Vit.K
X Placental barrier, safe during pregnancy Crosses barrier

Used mainly to initiate therapy Used maintenance therapy

Expensive Not expensive

Thrombolytics / Fibrinolytics -
 In response to stimuli (injury/stasis), t-PA is released from vascular endothelium.
 t-PA binds to fibrin bound plasminogen and converts to plasmin which breakdown the fibrin.
 These drugs breakdown the clot / thrombi by activating natural fibrinolytic system.
 e.g., streptokinase, urokinase & alteplase are plasminogen activators.
Uses-
1. Acute MI- IV adm reduces the mortality rate.
2. Deep vein thrombosis & pulmonary embolism.
Antifibrinolytics -

 These drugs block the conversion of plasminogen to plasmin & inhibit fibrinolytic activity.

Antifibrinolytics
Epsilon-amino Carpoic acid Used to control, bleeding due to overdose of fibrinolytics after
(EACA) tooth extraction, prostrate surgery, haematuria,
i.v/orally
Tranexamic acid More potent than EACA.
Oral/topical Used to control bleeding due to excessive fibrinolytic activity &
following tonsillectomy, prostatectomy, tooth extraction,
menorrhagia.
Antiplatelet drugs/ antithrombotics -
 Platelets forms –initial plug at the site of vascular damage & also involved in atherosclerosis.
 By X platelet aggregationthrombosis & atherosclerotic vascular disease can be prevented.
 E.g., aspirin, dipyrimidamole, sulphinpyrazone, ticlopidine.
Uses-
1. Acute MI-aspirin + Thrombolytics.
 Aspirin long term use reduces re-infraction in MI.
2. Angina pectoris/ unstable angina

3.In Prosthetic heart valves, valvular heart diseases & coronary by pass implants.

4. Cerebral thrombosis- in Pt’s with TIA- aspirin reduces the incidence of stroke & decreases
mortality.
Antiplatelet drugs/ antithrombotics -